Does Phototherapy Cause Neurotoxicity? A Study Using Bilirubin Photoisomer and a Blood-Brain Barrier Model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15886
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nara Medical University
• Principal Investigator: Uchida Yumiko 奈良県立医科大学, 医学部, 講師 (70319721)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ビリルビン / ビリルビン光学異性体 / 血液脳関門 / 細胞毒性

Outline of Final Research Achievements

Blood-brain barrier models consisting of infant Wister rat brain capillary endothelial cells were created, and lumirubin were tested (1) for passage into the brain and (2) for cytotoxicity.
Lumirubin was purified by exposure to blue-green light to final concentrations of 10, 25, and 50 μM, and 50 μM of unconjugated bilirubin was prepared as a control in 0.1% human albumin solution. The infant and adult models were compared in a blood-brain barrier model created with brain capillary endothelial cells from adult Wister rats. In the brain transfer test , lumirubin levels in the infant model migrated into the brain in a concentration-dependent manner, but not in the adult model. On the other hand, lumirubin showed no toxicity in the cytotoxicity test.

Free Research Field

新生児学

Academic Significance and Societal Importance of the Research Achievements

新生児黄疸に対する光療法の有効性は既に実証されている。一方、光療法に伴う超低出生体重児死亡率の増加や早産児のビリルビン慢性神経障害などが問題となっている。近年、光療法により産生されるビリルビン光学異性体(ルミルビン)による神経炎症惹起性についての報告があったが、ルミルビンの血液脳関門への移行性を検証した研究は未だない。本研究では幼若ラットを用いたモデルにおいてルミルビンが濃度依存性に血液脳関門を通過することを証明した初めての研究であり、今後、光療法と神経毒性との関係を調べる糸口になりうる研究であったと考える。